The present invention relates to novel methylthioribose analogues and their use as medicinal and biocidal agents.
5-Deoxy-5-methylthioribose (MTR) is a naturally occurring compound derived from 5'-deoxy-5'-methylthioadenosine (MTA). MTR is essential in the salvage of methionine in organisms containing the enzyme MTR kinase. MTR is a substrate for MTR kinase, and its carbohydrate and alkylthio moeities are recycled into methionine. Methionine, an essential amino acid, is required for DNA/RNA/protein synthesis.
U.S. Pat. No. 4,420,489 discloses 5-thio-D-ribose and 5-thio-2-deoxyribose (compounds in which the ring oxygen atom is replaced by a sulfur atom) as agents capable of preventing radiation damage.
U.S. Pat. Nos. 3,836,644; 3,767,800 and 4,481,196 disclose glycoside phosphate derivatives, some of which could be regarded in the broadest sense as analogs of MTR. In each case, the compounds demonstrate some physiological activity, but not biocidal activity.
U.S. Pat. No. 4,378,369 discloses that some mono- and diesters of 2,5-anhydro-D-mannitol are useful in treating diabetes. These compounds are similar, but not identical to MTR.
U.S. Pat. No. 4,243,663 discloses an adjuvant compound based on fructose instead of ribose.
U.S. Pat. No. 4,086,076 discloses tetrahydrofuranyl based compounds with fungicide and bacteriacide properties.
U.S. Pat. No. 2,840,587 discloses the synthesis of ethionine.
U.S. Pat. No. 4,080,465 discloses cyclic thio compounds.
Shapiro et al., Biochem. Biophys. Res. Comm., 102:302 (1981), discloses that MTR is the precursor of methionine in procaryotic microorganisms.
Schroeder et al., Can. J. Microbiol., 19, 1347 (1973), discloses the production of MTR in E. coli. The article further indicates that MTA is the precursor of MTR in procaryotic microorganisms.
Kikugawa et al., Tetrahedron Letters 2, 87-90 (1971), describes the synthesis of 5'-chloro-5'-deoxy-adenosine and similar compounds which serve as synthetic starting points for ethylthioadenosine (ETA). Biochem. Biophys. Acta., 320 357-362 (1973), describes the preparation of MTR.
Plant Physiology 71; 932 (1983) and Eur. J. Biochem. 87; 257 (1978) disclose isobutylthioribose.
Eur. Biochem., 87, 257 (1978) discloses 5-S-(2-methylpropyl)-5-thio-D-ribose.
Chem. Lett. 819 (1979) discloses orthophenylmethyl thioribose.
Agents for systemically treating fungal infections are known. Amphoterecin-B is frequently prescribed; however, it can cause undesirable side effects, e.g., renal failure.